Triazole compounds with dopamine-D3-receptor affinity

ABSTRACT

The invention relates to triazole compounds of formula (I), in which R1, R2, A and B have the meanings given in the description. The compounds provided for in the invention have a high affinity for the dopamine-D3-receptor and can therefore be used for the treatment of diseases which respond to the influence of dopamine-D3-ligands.

The invention relates to triazole compounds and to the use of these compounds. These compounds possess valuable therapeutic properties and can be used for treating diseases which respond to the influence of dopamine D₃ receptor ligands.

Compounds of the type which is under discussion here and which possess physiological activity are already known. Thus, WO 94/25013; 96/02520; 97/43262; 97/47602; 98/06699; 98/49145; 98/50363; 98/50364 and 98/51671 describe compounds which act on the dopamine receptors. DE 44 25 144 A, WO 96/30333, WO 97/25324, WO 97/40015, WO 97/47602, WO 97/17326, EP 887 350, EP 779 284 A and Bioorg. & Med. Chem. Letters 9 (1999) 2059-2064 disclose further compounds which possess activity as dopamine D₃ receptor ligands. U.S. Pat. Nos. 4,338,453; 4,408,049 and 4,577,020 disclose triazole compounds which possess antiallergic or antipsychotic activity. WO 93/08799 and WO 94/25013 describe compounds of the type which is under discussion here and which constitute endothelin receptor antagonists. Additional triazole compounds, which inhibit blood platelet aggregation and which have a hypotensive effect are described in Pharmazie 46 (1991), 109-112. Further triazole compounds which possess physiological activity are disclosed in EP 691 342, EP 556 119, WO 97/10210, WO 98/24791, WO 96/31512 and WO 92/20655.

Neurons obtain their information by way of G protein-coupled receptors, inter alia. There are a large number of substances which exert their effect by way of these receptors. One of them is dopamine.

A number of facts about the presence of dopamine, and its physiological function as a neurotransmitter, are known with certainty. Disturbances of the dopaminergic transmitter system result in diseases such as schizophrenia, depression and Parkinson's disease. These, and other, diseases are treated with drugs which interact with the dopamine receptors.

By 1990, two subtypes of dopamine receptor had been clearly defined pharmacologically, namely the D₁ and D₂ receptors.

More recently, a third subtype has been found, namely the D₃ receptor, which appears to mediate some of the effects of the antipsychotic and anti-Parkinson agents (J. C. Schwartz et al., The Dopamine D₃ Receptor as a Target for Antipsychotics, in Novel Antipsychotic Drugs, H. Y. Meltzer, Ed. Raven Press, New York 1992, pages 135-144; M. Dooley et al., Drugs and Aging 1998, 12, 495-514).

Since D₃ receptors are chiefly expressed in the limbic system, it is assumed that while a selective D₃ ligand would probably have the properties of known antipsychotic agents, it would not have their dopamine D₃ receptor-mediated neurological side-effects (P. Sokoloff et al., Localization and Function of the D₃ Dopamine Receptor, Arzneim. Forsch./Drug Res. 42(1), 224 (1992); P. Sokoloff et al. Molecular Cloning and Characterization of a Novel Dopamine Receptor (D₃) as a Target for Neuroleptics, Nature, 347, 146 (1990)).

Surprisingly, it has now been found that certain triazole compounds exhibit a high affinity for the dopamine D₃ receptor and a low affinity for the D₂ receptor. These compounds are consequently selective D₃ ligands.

The present invention relates, therefore, to the compounds of the formula I:

where

R¹ is H, C₁-C₆-alkyl, which may be substituted by OH, OC₁-C₆-alkyl, halogen or phenyl, C₃-C₆-cycloalkyl or phenyl;

R² is H, C₁-C₆-alkyl, which may be substituted by OH, OC₁-C₆-alkyl, halogen or phenyl, C₁-C₆-alkoxy, C₁-C₆-alkylthio, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₆-cycloalkyl, halogen, CN, COOR³, CONR³R⁴, NR³R⁴, SO₂R³, SO₂NR³R⁴, or an aromatic radical which is selected from phenyl, naphthyl and a 5- or 6-membered heterocyclic radical having 1, 2, 3 or 4 heteroatoms which are selected, independently of each other, from O, N and S, with it being possible for the aromatic radical to have one or two substituents which are selected, independently of each other, from C₁-C₆-alkyl, which may be substituted by OH, OC₁-C₆-alkyl, halogen or phenyl, C₁-C₆-alkoxy, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₆-cycloalkyl, halogen, CN, COR³, NR³R⁴, NO₂, SO₂R³, SO₂NR³R⁴ and phenyl which may be substituted by one or two radicals which are selected, independently of each other, from C₁-C₆-alkyl, C₁-C₆-alkoxy, NR³R⁴, CN, CF₃, CHF₂ or halogen;

R³ and R⁴ are, independently of each other, H, C₁-C₆-alkyl, which may be substituted by OH, OC₂-C₆-alkyl, halogen or phenyl, or phenyl;

A is C₄-C₁₀-alkylene or C₃-C₁₀-alkylene which comprises at least one group Z which is selected from O, S, CONR³, COO, CO, C₃-C₆-cycloalkyl and a double or triple bond;

B is a radical of the following formulae (a) and (b):

X is CH₂ or CH₂CH₂;

Y is CH₂ or O;

R⁶ and R⁷ are, independently of each other, selected from H, C₁-C₆-alkyl, which may be substituted by halogen, OH, C₁-C₆-alkoxy, C₂-C₆-alkenyl, halogen, CN, NO₂, SO₂R³, SO₂NR³R⁴, CONR³R⁴, NHSO₂R³ and NR³R⁴;

and the salts thereof with physiologically tolerated acids.

The compounds according to the invention are selective dopamine D₃ receptor ligands which act in the limbic system in a regioselective manner and which, as a result of their low affinity for the D₂ receptor, have fewer side-effects than do the classic neuroleptic agents, which are D₂ receptor antagonists. The compounds can therefore be used for treating diseases which respond to dopamine D₃ ligands, i.e. they are effective for treating those diseases in which affecting (modulating) the dopamine D₃ receptors leads to an improvement in the clinical picture or to the disease being cured. Examples of such diseases are diseases of the cardiovascular system and the kidneys, diseases of the central nervous system, in particular schizophrenia, affective disorders, neurotic stress and somatoform disorders, psychoses, parkinsonism, attention deficit disorders, hyperactivity in children, epilepsy, amnesic and cognitive disorders such as learning and memory impairment (impaired cognitive function), anxiety states, dementia, delirium, personality disorders, sleep disturbances (e.g. restless legs syndrome), disorders of sex life (male impotence), eating disorders and addictive disorders. Moreover they are useful in the treatment of stroke.

Addictive disorders include the psychological disorders and behavioral disturbances caused by abuse of psychotropic substances such as pharmaceuticals or drugs, and other addictive disorders such as compulsive gambling (impulse control disorders not elsewhere classified). Addictive substances are, for example: opioids (e.g. morphine, heroin, codeine); cocaine; nicotine; alcohol; substances which interact with the GABA chloride channel complex, sedatives, hypnotics or tranquilizers, e.g. benzodiazepines; LSD; cannabinoids; psychomotor stimulants such as 3,4-methylenedioxy-N-methylamphetamine (ecstasy); amphetamine and amphetamine-like substances such as methylphenidate or other stimulants including caffeine. Addictive substances of particular concern are opioids, cocaine, amphetamine or amphetamine-like substances, nicotine and alcohol.

The compounds according to the invention are preferably employed for treating affective disorders; neurotic, stress and somatoform disorders and psychoses, e.g. schizophrenia.

Within the context of the present invention, the following expressions have the meanings given in conjunction with them:

Alkyl (also in radicals such as alkoxy, alkylthio, alkylamino etc.) is a straight-chain or branched alkyl group having from 1 to 6 carbon atoms and, in particular from 1 to 4 carbon atoms. The alkyl group can have one or more substituents which are selected, independently of each other, from OH, OC₁-C₆-alkyl, halogen or phenyl. In the case of a halogen substituent, the alkyl group can, in particular, encompass, 1, 2, 3 or 4 halogen atoms which can be located on one or more C atoms, preferably in the α or ω position. CF₃, CHF₂, CF₂Cl or CH₂F are particularly preferred.

Examples of an alkyl group are methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, t-butyl, etc.

Cycloalkyl is, in particular, C₃-C₆-cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

Alkylene radicals are straight-chain or branched. If A does not have a group Z, A then comprises from 4 to 10 carbon atoms, preferably from 4 to 8 carbon atoms. The chain between the triazole nucleus and group B then has at least four carbon atoms. If A has at least one of said Z groups, A then comprises from 3 to 10 carbon atoms, preferably from 3 to 8 carbon atoms.

If the alkylene groups comprise at least one of the Z groups, this or these groups can then be arranged in the alkylene chain at an arbitrary site or in position 1 or 2 of the A group (seen from the triazole radical). The radicals CONR² and COO are preferably arranged such that the carbonyl group is in each case facing the triazole ring. Particular preference is given to the compounds of the formula I in which A is —Z—C₃-C₆-alkylene, in particular —Z—CH₂CH₂CH₂—, —Z—CH₂CH₂CH₂CH₂—, —Z—CH₂CH═CHCH₂—, —Z—CH₂C(CH₃)═CHCH₂—,

—Z—CH₂CH(CH₃)CH₂—or a linear —Z—C₇-C₁₀-alkylene radical, with Z being bonded to the triazole ring. Z is preferably CH₂, O and in particular S. Preference is additionally given to A being —(CH₂)₄—, —(CH₂)₅—, —CH₂CH₂CH═CHCH₂—,

—CH₂CH₂C(CH₃)═CHCH₂— or —CH₂CH₂CH(CH₃)CH₂—.

Halogen is F, Cl, Br or I, preferably F or Cl.

R¹ is preferably H, C₁-C₆-alkyl or C₃-C₆-cycloalkyl.

If R² is an aromatic radical, this radical is then preferably one of the following radicals:

where

R⁹ to R¹¹ are H or the abovementioned substituents of the aromatic radical,

R¹² is H, C₁-C₆-alkyl or phenyl, and

T is N or CH.

If the phenyl radical is substituted, the substituents are preferably in the m position or the p position.

The aromatic radical is particularly preferably a group of the formula:

where R⁹, R¹⁰ and R¹² have the abovementioned meanings. The indicated phenyl, pyridyl, thiazolyl and pyrrole radicals are particularly preferred.

The radicals R⁹ to R¹¹ are preferably H, C₁-C₆alkyl, OR³, CN, phenyl, which may be substituted by C₁-C₆-alkyl, C₁-C₆-alkoxy or halogen, CF₃ and halogen, and are, in particular, H, C₁-C₆-alkyl, OR³ and halogen. In this context, R³ has the abovementioned meanings.

Particularly preferably, R² is H, C₁-C₆-alkyl, NR³R⁴ (R³ and R⁴ are, independently of each other, H or C₁-C₆-alkyl), phenyl or a 5-membered aromatic heterocyclic radical which has 1 or 2 heteroatoms which are independently selected from N, S and O. The heterocyclic radical is preferably a pyrrole radical or a pyridine radical.

X and/or Y are preferably CH₂.

A is preferably C₄-C₁₀-alkylene or C₃-C₁₀-alkylene which comprises at least one group Z which is selected from O, S, COO, CO and a double bond.

Preferably, at least one of the radicals R⁶, R⁷ and R⁸ is H.

The radicals R⁶ and R⁷ are preferably, and independently of each other, selected from H, C₁-C₆-alkyl, OH, C₁-C₆-alkoxy, C₁-C₆-alkylthio-C₁-C₆-alkyl, halogen, CN, NO₂, SO₂R³, SO₂NR³R⁴ and CONR³R⁴. Particularly preferably, the phenyl group has one or two substituents, i.e. one or two of the radicals R⁶ and R⁷ is/are C₁-C₆-alkyl, OH, halogen, CN, SO₂NR³R⁴ ₁ NO₂ or CF₃.

Particular preference is given to the compounds of formula I where

R¹ is H, C₁-C₆-alkyl or phenyl,

R² is H, C₁-C₆-alkyl, phenyl, thienyl, furanyl, pyridyl, pyrrolyl, thiazolyl or pyrazinyl,

A is —SC₃-C₁₀-alkylene which can comprise a double bond, and

R⁶ and R⁷ are selected from H, C₁-C₆-alkyl, C₁-C₆-alkoxy, halogen, SO₂NR³R⁴; CN, NO₂ and CF₃.

The invention also encompasses the acid addition salts of the compounds of the formula I with physiologically tolerated acids. Examples of suitable physiologically tolerated organic and inorganic acids are hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, oxalic acid, maleic acid, fumaric acid, lactic acid, tartaric acid, adipic acid or benzoic acid. Other acids which can be used are described in Fortschritte der Arzneimittelforschung [Advances in pharmaceutical research], Volume 10, pages 224 ff., Birkhäuser Verlag, Basle and Stuttgart, 1966.

The compounds of the formula I can exhibit one or more centers of asymmetry. The invention therefore includes not only the racemates but also the relevant enantiomers and diastereomers.

The respective tautomeric forms are also included in the invention.

The process for preparing the compounds of the formula I consist in

a) reacting a compound of the formula (II)

 where Y¹ is a customary leaving group, such as Hal, alkylsulfonyloxy, arylsulfonyloxy, etc., with a compound of the formula (III)

HB  (III);

 or

b) reacting a compound of the formula (IV)

 where Z¹ is O or S, and A¹ is C₁-C₁₀-alkylene or a bond, with a compound of the formula (V),

Y¹—A²—B  (V)

where Y¹ has the abovementioned meaning and A² is C₂-C₁₀-alkylene, with A¹ and A² together having from 3 to 10 C atoms and A¹ and/or A² where appropriate comprising at least one group Z; or

c) reacting a compound of the formula (VI)

 where Y¹ and A¹ have the abovementioned meanings, with a compound of the formula (VII)

H—Z¹—A—B  (VII)

where Z¹ has the abovementioned meanings; or

d) reversing the polarity of a compound of the formula (VIII)

 using reagents which are known from the literature, such as 1,3-propanedithiol, KCN/water, TMSCN (trimethylsilyl cyanide) or KCN/morpholine, as described, for example, in

Albright Tetrahedron, 1983, 39, 3207 or

D. Seebach Synthesis 1969, 17 und 1979, 19 or

H. Stetter Angew. Chem. Int. Ed. 1976, 15, 639 or

van Niel et al. Tetrahedron 1989, 45, 7643

Martin et al. Synthesis 1979, 633,

 to give the products (VIIIa) (using 1,3-propanedithiol by way of example)

 and then chain-elongating with compounds of the formula (IX)

Y¹—A³—B  (IX)

where Y¹ has the abovementioned meaning and A³ is C₃-C₉-alkylene which can contain a group Z,

 with compounds of the formula (Ia)

 where Z² is CO or a methylene group, and Z² and A² have together from 4 to 10 C atoms, being obtained after deprotecting or reducing, or

e) reacting a compound of the formula (VIII) with a compound of the formula (X)

Y²—A—B  (X)

 where Y² is a phosphorane or a phosphonic ester, in analogy with customary methods, as described, for example, in Houben Weyl “Handbuch der Organischen Chemie” [Textbook of Organic Chemistry], 4th Edition, Thieme Verlag Stuttgart, Volume V/lb p. 383 ff, or Vol. V/1c p. 575 ff, or

f) reacting a compound of the formula (XI)

 where Q is H or OH, with a compound of the formula III under reductive conditions in analogy with methods known from the literature, for example as described in J. Org. Chem. 1986, 50, 1927; or WO 92/20655.

The process for preparing a compound of the formula I where A comprises the groups COO or CONR³ consists in reacting a compound of the formula (XII)

 where Y³ is OH, OC₁-C₄-alkyl, Cl or, together with CO, an activated carboxyl group, and A⁴ is C₀-C₉-alkylene, with a compound of the formula (XIII)

B—A—Z³  (XIII)

where Z³ is OH or NHR³.

Compounds of the type (XIV)

can be synthesized by alkylating compounds of the formula (IV) with compounds of the formula (XV),

to give compounds of the formula (XVI),

subsequently carrying out hydrazinolysis to give compounds of the type (XVII)

Compounds of the formula XVII (or XIV) can also be obtained by reacting compounds of the formula II with azides, such as sodium azide, and then reducing, as described, for example, in H. Staudinger, Helv. Chim. Acta 1985, 2, 635 or R. Carrie, Bull. Chem. Soc. Fr. 1985, 815.

Compounds of the general formulae B-H can be prepared as described, for example, in

S. Smith et al., Bioorg. Med. Chem. Lett. 1998, 8, 2859;

WO 97/47602, WO 920655 and W098/24791, or

J. Med. Chem. 1987, 30, 2111 and 2208.

The compounds of the formula (IV) type are either known or can be prepared using known methods, as described, for example, in A. R. Katritzky, C. W. Rees (ed.) “Comprehensive Heterocyclic Chemistry”, Pergamon Press, or “The Chemistry of Heterocyclic Compounds” J. Wiley & Sons Inc. N.Y. and the literature which is cited therein, or in S. Kubota et al. Chem. Pharm. Bull. 1975, 23, 955 or Vosilevskii et al. Izv. Akad. Nauk. SSSR Ser. Khim. 1975, 23, 955.

In the above formulae, R¹, R², R⁶, R⁷, A, B, X and Y have the meanings given in connection with formula I.

The compounds according to the invention, and the starting materials and the intermediates, can also be prepared in analogy with the methods which are described in the patent publications which were mentioned at the outset.

The above-described reactions are generally effected in a solvent at temperatures of between room temperature and the boiling temperature of the solvent employed. Examples of solvents which can be used are esters, such as ethyl acetate, ethers, such as diethyl ether or tetrahydrofuran, dimethylformamide, dimethyl sulfoxide, dimethoxyethane, toluene, xylene, acetonitrile, ketones, such as acetone or methyl ethyl ketone, or alcohols, such as ethanol or butanol.

If desired, the reactions can be carried out in the presence of an acid-binding agent. Suitable acid-binding agents are inorganic bases, such as sodium carbonate or potassium carbonate, or sodium hydrogencarbonate or potassium hydrogencarbonate, sodium methoxide, sodium ethoxide, sodium hydride, or organometallic compounds, such as butyl lithium or alkyl magnesium compounds, or organic bases, such as triethylamine or pyridine. The latter can also simultaneously serve as the solvent.

Process (f) is effected under reducing conditions, e.g. using sodium borohydride, sodium cyanoborohydride or triacetoxy borohydride, where appropriate in an acid medium or in the presence of a Lewis acid, such as zinc chloride, or by way of catalytic hydrogenation.

The crude product is isolated in a customary manner, for example by means of filtering, distilling off the solvent or extracting from the reaction mixture, etc. The resulting compounds can be purified in a customary manner, for example by recrystallization from a solvent, by chromatography or by converting into an acid addition compound.

The acid addition salts are prepared in a customary manner by mixing the free base with the corresponding acid, where appropriate in solution in an organic solvent, for example a lower alcohol, such as methanol, ethanol or propanol, an ether, such as methyl tert-butyl ether, a ketone, such as acetone or methyl ethyl ketone, or an ester, such as ethyl acetate.

For treating the abovementioned diseases, the compounds according to the invention are administered orally or parenterally (subcutaneously, intravenously, intramuscularly or intraperitoneally) in a customary manner. The administration can also be effected through the nasopharyngeal space using vapors or sprays.

The dosage depends on the age, condition and weight of the patient and on the type of administration. As a rule, the daily dose of active compound is from about 10 to 1000 mg per patient and day when administered orally and from about 1 to above 500 mg per patient and day when administered parenterally.

The invention also relates to pharmaceuticals which comprise the compounds according to the invention. In the customary pharmacological administration forms, these pharmaceuticals are present in solid or liquid form, for example as tablets, film tablets, capsules, powders, granules, sugar-coated tablets, suppositories, solutions or sprays. In this context, the active compounds can be worked up together with the customary pharmacological auxiliary substances, such as tablet binders, fillers, preservatives, tablet disintegrants, flow-regulating agents, plasticizers, wetting agents, dispersants, emulsifiers, solvents, retarding agents, antioxidants and/or propellent gases (cf. H. Sucker et al., Pharmazeutische Technologie, Thieme-Verlag, Stuttgart, 1978). The resulting administration forms normally comprise the active compound in a quantity of from 1 to 99% by weight.

The following examples serve to explain the invention without limiting it.

EXAMPLE 1 (cis/trans) 9-Bromo-3-{3-[(4-methyl-5-phenyl-4H-1,2,4-triazol-3-yl)sulfanyl]propyl}-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indole

Synthesis of the Starting Materials

1A Methyl (8-bromo-2-oxo-1,2,3,4-tetrahydronaphthalen-1-yl)-acetate

33 ml of 2M lithiumdiisopropylamide were added to a solution of 13.5 g (60 mmol) of 8-bromotetralone in 470 ml of THF at −30° C. under a protective gas atmopshere and, after stirring, a solution of 11 g (72.mmol) of methylbromoacetate in 100 ml of THF was added dropwise. The mixture was worked up after 18 h at room temperature by adding 10 ml of concentrated hydrochloric acid at 0° C. The solvent was removed in vacuo, and the residue was taken up in water and extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and concentrated; the residue was purified by column chromatography (silica gel, mobile phase: methylene chloride).

Yield: 13.7 g (46 mmol); 77% of theory C₁₃H₁₃BrO₃ (297.2) MS: 296/298 [M⁺]

1B (cis/trans) 9-Bromo-3-{3-[(4-methyl-5-phenyl-4H-1,2,4-triazol-3-yl)sulfanyl]propyl}-1,3,3a,4,5,9b-hexahydro-2H-benzo[e]indol-2-one

To a solution of 0.9 g (3.6 mmol) of 3-[(4-methyl-5-phenyl-4H-1,2,4-triazol-3-yl)sulfanyl]propylamine and 0.7 g (2.4 mmol) of the above compound in 10 ml of THF/methanol=1/1 at 0° C. were added 0.8 ml of glacial acetic acid (pH 4-5) and then 0.2 mg (2.4 mmol) of sodium cyanoborohydride, and the mixture was stirred at room temperature for 72 hours. Workup entailed addition of 20% strength sodium hydroxide solution, concentration in vacuo and taking out the residue with dichloromethane. The organic phase was washed with water, dried over sodium sulfate, filtered and concentrated, after which the residue was purified by column chromatography (silica gel, mobile phase: methylene chloride with 3-5% methanol).

Yield: 0.6 g(1.1mmol); 47% of theory ¹H-NMR (CDC13): δ=1.8-2.3 (m, 6H); 2,7 (mbr, 2H); 3.1-3.4 (m, 4H); 3.6 (s, 3H); 3.8-4.0 (m, 2H); 4.1 (m, 1H); 7.1 (m, 2H); 7.4 (d, 1H); 7.5 (m, 3H);. 7.7 (m, 2H).

C₂₄H₂₅BrN₄OS (497.5).

Preparation of the Final Product

560 mg (1.1 mmol) of the compound prepared in 1B and dissolved in 2 ml of THF were added to 1.9 ml of a 1M borane/THF solution while cooling in ice and under protective gas, and the mixture was heated to boiling for 1 hour. After the reaction was complete, 1 ml of 10% strength hydrochloric acid was added, the mixture was concentrated, the residue was taken up in water and, after making alkaline, extracted with dichloromethane. The combined organic phases were dried over sodium sulfate, filtered and concentrated. The crude product was purified by chromatography (silica gel, mobile phase: methylene chloride with 3-5% methanol).

Yield: 40 mg (0.1 mmol); 8% of theory ¹H-NMR (CDC13): δ=1.3-1.5 (m, 2H); 1.9 (m, 1H); 2.0 (m, 2H); 2.2 (m, 1H); 2.4-2.5 (m, 2H); 2.6 (m, 1H); 2.8-3.0 (m, 3H); 3.1 (t, 1H);,3.2-3.4 (2m, 2H); 3.6 (m, 4H); 6.9 (t, 1H); 7.0 (d, 1H); 7.4 (d, 1H); 7.5 (m, 3H); 7.7 (m, 2H). C₂₄H₂₇BrN₄S (482.9).

The following was prepared in an analogous manner in principle:

EXAMPLE 2 (cis/trans) 7-tert-Butyl-3-{3-[(4-methyl-5-phenyl-4H-1,2,4-triazol-3-yl)sulfanyl]propyl}-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indole

C₂₈H₃₆N₄S (460.7) MS: 461 [M⁺]

EXAMPLE 3 (cis/trans) 9-Bromo-3-{3-[(4-methyl-5-(thien-3-yl)-4H-1,2,4-triazol-3-yl)sulfanyl]propyl}-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indole EXAMPLE 4 (cis/trans) 3-{3-[(4-methyl-5-phenyl-4H-1,2,4-triazol-3-yl)-butyl}-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indole

The following compounds can be prepared in an analogous way in principle:

TABLE 1

Ex. R¹ R² A Y R⁶ R⁷*  5 Et 2,5-Di-methyl-furanyl-3- S—(CH₂)₃— CH₂ 7-tert-butyl H  6 Me 2-Pyrazinyl- O—(CH₂)₃— CH₂ H  7 Propyl 3-Br-Pyridin-5-yl- S—(CH₂)₃— CH₂ 7-carboxamido  8 Phenyl Cyano S—(CH₂)₃— CH₂ H  9 Ethyl 3-Jod-phenyl (CH₂)₄— O 7-tert-butyl  10 Me 3-Pyrrolyl S—(CH₂)₃— CH₂ 8-fluoro  11 butyl 2,5-Di-methyl-furanyl-3- S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy  12 Me 2-Pyrazinyl- S—(CH₂)₃— CH₂ 7-tert-butyl  13 cycPropyl Pyridin-4-yl- S—(CH₂)₃— CH₂ 8-fluoro  14 Ethyl 4-Methylthiazol-5-yl S—CH₂—C(CH₃)═CH—CH₂— CH₂ 7-tert-butyl  15 Me 4-Methoxyphenyl (CH₂)₄— CH₂ 9-fluoro  16 Me 4-Jod-phenyl S—(CH₂)₃— CH₂ 7-tert-butyl  17 Me 2-Thienyl (CH₂)₄— CH₂ H  18 Propyl 4-Imidazolyl- S—(CH₂)₃— CH₂ 7-carboxamido  19 Me 2,5-Di-methyl-furanyl-3- S—(CH₂)₃— CH₂ H  20 Propyl 4-Methylthiazol-5-yl CONH—(CH₂)₄— CH₂ 7-methyl  21 Me Phenyl S—CH₂—C(═CH₂)—CH₂ O 8-bromo  22 Me N-Methyl-2-Pyrrolyl- (CH₂)₄— O 9-methyl  23 Me Tetrazolyl- S—(CH₂)₃— CH₂ 8-fluoro  24 Me 2-Me-4-Oxazolyl- S—(CH₂)₃— O 7-tert-butyl  25 Me Oxadiazol-2-yl S—(CH₂)₃— CH₂ H  26 Me 3-Cyano-phenyl S—(CH₂)₃— CH₂ 6-methoxy  27 isoPropyl 3-Br-Pyridin-5-yl- S—(CH₂)₃— CH₂ 8-trifluoromethoxy  28 Me 2-Thienyl S—CH₂—C(═CH₂)—CH₂ CH₂ 8-fluoro  29 Me 2-Aminothiazol-4yl- S—(CH₂)₃— CH₂ 6-methoxy  30 Me 3-Cyano-phenyl S—(CH₂)₃— O H  31 Me 3-Thienyl S—(CH₂)₃— CH₂ 7-tert-butyl  32 Me 4-Methylthiazol-5-yl S—(CH₂)₃— O 7-nitro  33 Me Cyclohexyl- S—(CH₂)₃— CH₂ 8-fluoro  34 isoPropyl 2-Aminothiazol-4yl- S—(CH₂)₃— CH₂ 8-trifluoromethoxy  35 Me 3-Jod-phenyl (CH₂)₄— O 7-tert-butyl  36 butyl Pyridin-4-yl- S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy  37 Me 4-Methoxyphenyl S—(CH₂)₃— CH₂ 7-cyano  38 Hexyl 4-Imidazolyl- S—(CH₂)₃— CH₂ 6-methoxy  39 Ethyl Pyridin-3-yl- S—(CH₂)₆— CH₂ 7-tert-butyl  40 Me 4-Methoxyphenyl (CH₂)₄— O 9-fluoro  41 Propyl N-Methyl-2-Pyrrolyl- CONH—(CH₂)₄— CH₂ 8-trifluoromethoxy  42 cycPropyl 4-Methoxyphenyl S—(CH₂)₃— CH₂ 8-fluoro  43 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— CH₂ 7-nitro  44 Me 3-Jod-phenyl O—(CH₂)₃— O H  45 Me N-Propyl-tetrazolyl- S—(CH₂)₃— O H  46 isoButyl Oxadiazol-2-yl S—(CH₂)₃— O 7-tert-butyl  47 Ethyl Pyridin-3-yl- (CH₂)₄— O H  48 Me 2-Thienyl S—(CH₂)₃— O 7-nitro  49 Me Phenyl CO—CH₂—C(═CH₂)—CH₂ O 7-tert-butyl  50 Me Pyridin-3-yl- S—(CH₂)₃— CH₂ 6-methoxy  51 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— CH₂ H  52 Me Pyridin-3-yl- S—(CH₂)₃— O 7-cyano  53 butyl 3-Cyano-phenyl S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy  54 Me 2-Thienyl S—(CH₂)₈— O 6-methoxy  55 Me 2-Pyrazinyl- S—(CH₂)₃— O 7-nitro  56 Ethyl 2-Thienyl (CH₂)₄— O H  57 Ethyl Phenyl S—CH₂—C(CH₃)═CH—CH₂— O 7-tert-butyl  58 Me 4-Methoxyphenyl S—(CH₂)₃— CH₂ 7-tert-butyl  59 Me 3-Br-Pyridin-5-yl- S—(CH₂)₃— CH₂ H  60 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— O H  61 Me N-Propyl-tetrazolyl- S—(CH₂)₃— CH₂ 8-trifluoromethoxy  62 butyl 3-Br-Pyridin-5-yl- S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy  63 Ethyl Phenyl S—CH₂—C(CH₃)═CH—CH₂— O 7-sulfonamido  64 Me 2-Thienyl S—(CH₂)₃— CH₂ 7-sulfonamido  65 Me Pyridin-3-yl- S—(CH₂)₈— CH₂ 8-trifluoromethoxy  66 Me 3-Jod-phenyl S—(CH₂)₃— CH₂ 8-fluoro  67 Me Phenyl O—(CH₂)₄— O 8-iod  68 Me Pyridin-3-yl- S—(CH₂)₈— O 8-trifluoromethoxy  69 isoPropyl 3-Cyano-phenyl S—(CH₂)₃— CH₂ 8-trifluoromethoxy  70 butyl N-Propyl-tetrazolyl- S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy  71 Ethyl Pyridin-3-yl- S—CH₂—CH═CH—CH₂— CH₂ 8-fluoro  72 Me 3-Br-Pyridin-5-yl- S—(CH₂)₃— O H  73 Phenyl Methylamino S—(CH₂)₃— CH₂ 8-fluoro  74 Ethyl Phenyl CO—(CH₂)₃— O H  75 Me Phenyl S—(CH₂)₁₀— CH₂ 7-methyl  76 cycPropyl 4-Imidazolyl- S—(CH₂)₃— CH₂ 8-fluoro  77 Me 2-Thienyl S—(CH₂)₃— O H  78 Me 3-Jod-phenyl O—(CH₂)₃— CH₂ H  79 Et 3-Benzthienyl- S—(CH₂)₃— CH₂ 7-tert-butyl  80 Me 4-Methoxyphenyl S—(CH₂)₃— CH₂ 7-nitro  81 Ethyl Phenyl S—(CH₂)₃— O 7-nitro  82 Ethyl 2-Thienyl CO—(CH₂)₃— CH₂ H  83 cycPropyl 3-Cyano-phenyl S—(CH₂)₃— CH₂ 8-fluoro  84 Propyl Phenyl CONH—(CH₂)₅— CH₂ 7-methyl  85 Me 2,5-Di-methyl-furanyl-3- S—(CH₂)₃— O H  86 Et N-Propyl-tetrazolyl- S—(CH₂)₃— CH₂ 7-tert-butyl  87 Ethyl 2-Aminothiazol-4yl- S—(CH₂)₃— O H  88 Me Tetrazolyl- S—(CH₂)₃— CH₂ H  89 Propyl Phenyl COO—(CH₂)₄— CH₂ 7-methyl  90 Propyl 2-Pyrazinyl- COO—(CH₂)₄— CH₂ 8-trifluoromethoxy  91 Propyl Pyridin-3-yl- CONH—(CH₂)₄— CH₂ 7-methyl  92 Me Oxadiazol-2-yl S—(CH₂)₃— CH₂ 8-fluoro  93 butyl 3-Benzthienyl- S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy  94 Me 4-Methylthiazol-5-yl (CH₂)₄— CH₂ 9-methyl  95 Me 4-Methylthiazol-5-yl (CH₂)₄— O 9-methyl  96 Me 3-Jod-phenyl S—(CH₂)₃— CH₂ H  97 Me 2-Thienyl (CH₂)₄— O H  98 isoPropyl 5-Methyl imidazol-4-yl- S—(CH₂)₃— O 8-trifluoromethoxy  99 Me N-Methyl-2-Pyrrolyl- S—(CH₂₎ ₃— O 7-cyano 100 Me Phenyl S—(CH₂)₃— CH₂ 7-cyano 101 isoButyl Tetrazolyl- S—(CH₂)₃— O H 102 Me Phenyl CO—CH₂—C(═CH₂)—CH₂ CH₂ 7-tert-butyl 103 Me 2-Pyrazinyl- S—(CH₂)₃— CH₂ 6-methoxy 104 Me 2-Pyrazinyl- S—(CH₂)₃— CH₂ 7-nitro 105 Ethyl Pyridin-3-yl- S—CH₂—CH═CH—CH₂— O 8-fluoro 106 Me 4-Methylthiazol-5-yl S—(CH₂)₃— O H 107 Me 2-Pyrazinyl- (CH₂)₄— O 7-methyl 108 Phenyl 4-Imidazolyl- S—(CH₂)₃— O H 109 Me Pyridin-4-yl- S—(CH₂)₃— CH₂ 8-trifluoromethoxy 110 Me 2-Thienyl S—(CH₂)₇— CH₂ 8-trifluoromethoxy 111 Hexyl 3-Benzthienyl- S—(CH₂)₃— CH₂ 6-methoxy 112 cycPropyl Amino S—(CH₂)₃— CH₂ 8-fluoro 113 Me 2-Thienyl S—(CH₂)₃— O 7-cyano 114 Me Oxadiazol-2-yl S—(CH₂)₃— CH₂ 7-tert-butyl 115 Ethyl 4-Methylthiazol-5-yl S—CH₂—C(═CH₂)—CH₂ O 7-sulfonamido 116 Me 2-Thienyl S—(CH₂)₃— CH₂ 8-fluoro 117 Me Methylamino S—(CH₂)₃— CH₂ H 118 Me 3-Pyrrolyl S—(CH₂)₃— CH₂ 7-tert-butyl 119 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— CH₂ 7-sulfonamido 120 butyl 2-Aminothiazol-4yl- S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy 121 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— O 7-nitro 122 isoPropyl Phenyl S—(CH₂)₃— O 7-sulfonamido 123 Me 2-Me-4-Oxazolyl- S—(CH₂)₃— CH₂ 6-methoxy 124 cycPropyl Methylamino S—(CH₂)₃— CH₂ 7-tert-butyl 125 isoPropyl Cyano S—(CH₂)₃— CH₂ 6-methoxy 126 Me Phenyl S—(CH₂)₃— CH₂ 6-methoxy 127 Propyl 3-Cyano-phenyl S—(CH₂)₃— CH₂ 7-carboxamido 128 Propyl Phenyl CONH—(CH₂)₅— O 7-methyl 129 Ethyl 3-Jod-phenyl S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy 130 Ethyl 4-Methylthiazol-5-yl S—(CH₂)₆— O 7-cyano 131 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy 132 Me 2-Aminothiazol-4yl- S—(CH₂)₃— CH₂ H 133 Me Oxadiazol-2-yl S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy 134 Me 2-Me-4-Oxazolyl- S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy 135 Me Pyridin-3-yl- (CH₂)₄— CH₂ H 136 Ethyl Phenyl S—CH₂—C(CH₃)═CH—CH₂— CH₂ 7-tert-butyl 137 Me Phenyl (CH₂)₄— O H 138 Et 4-Imidazolyl- S—(CH₂)₃— CH₂ 7-tert-butyl 139 isoPropyl 3-Benzthienyl- S—(CH₂)₃— CH₂ 8-trifluoromethoxy 140 Me 2-Pyrazinyl- S—(CH₂)₃— O 7-cyano 141 Hexyl Amino S—(CH₂)₃— CH₂ 6-methoxy 142 Me 5-Methyl imidazol-4-yl- S—(CH₂)₃— CH₂ 6-methoxy 143 Me Pyridin-3-yl- S—(CH₂)₃— CH₂ 7-tert-butyl 144 Me Pyridin-3-yl- S—(CH₂)₃— CH₂ 8-fluoro 145 cycPropyl N-Propyl-tetrazolyl- S—(CH₂)₃— CH₂ 8-fluoro 146 Me 2-Me-4-Oxazolyl- S—(CH₂)₃— CH₂ H 147 Me 3-Jod-phenyl S—(CH₂)₃— CH₂ 7-nitro 148 Propyl 4-Methoxyphenyl COO—(CH₂)₃— CH₂ 7-sulfonamido 149 Me Pyridin-3-yl- (CH₂)₄— OH H 150 Me 2-Thienyl O—(CH₂)₄— CH₂ 7-tert-butyl 151 butyl 5-Methyl imidazol-4-yl- S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy 152 isoButyl Methylamino S—(CH₂)₃— O H 153 Hexyl N-Propyl-tetrazolyl- S—(CH₂)₃— CH₂ 6-methoxy 154 Phenyl Amino S—(CH₂)₃— O H 155 Me Phenyl CO—CH₂—C(═CH₂)—CH₂ O 7-tert-butyl 156 Me 2-Pyrazinyl- S—(CH₂)₃— O H 157 Me 3-Pyrrolyl S—(CH₂)₃— CH₂ 6-methoxy 158 Me 2-Me-4-Oxazolyl- S—(CH₂)₃— CH₂ 8-fluoro 159 Me Phenyl S—(CH₂)₃— O H 160 Ethyl Pyridin-3-yl- S—(CH₂)₆— O 7-tert-butyl 161 Me 3-Jod-phenyl S—(CH₂)₃— CH₂ 7-sulfonamido 162 Me 3-Pyrrolyl S—(CH₂)₃— O H 163 isoPropyl 3-Pyrrolyl S—(CH₂)₃— CH₂ 8-trifluoromethoxy 164 Me Pyridin-3-yl- S—(CH₂)₃— O 7-tert-butyl 165 Me 2-Thienyl S—(CH₂)₃— O 7-nitro 166 butyl 4-Imidazolyl- S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy 167 Me Tetrazolyl- S—(CH₂)₃— CH₂ 7-tert-butyl 168 Me Phenyl O—(CH₂)₄— CH₂ 7-tert-butyl 169 Me Phenyl S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy 170 Me N-Methyl-2-Pyrrolyl- (CH₂)₄— CH₂ 9-methyl 171 Me 3-Jod-phenyl (CH₂)₄— CH₂ 7-tert-butyl 172 Me 5-Methyl imidazol-4-yl- S—(CH₂)₃— CH₂ 8-fluoro 173 Me 2-Aminothiazol-4yl- S—(CH₂)₃— CH₂ 7-tert-butyl 174 Me 4-Methoxyphenyl S—(CH₂)₃— O 7-nitro 175 Me Pyridin-4-yl- S—(CH₂)₃— O H 176 Me 2-Thienyl S—(CH₂)₃— CH₂ 7-cyano 177 Me 2-Thienyl S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy 178 Me 2-Pyrazinyl- O—(CH₂)₃— O H 179 isoPropyl 5-Methyl imidazol-4-yl- S—(CH₂)₃— CH₂ 8-trifluoromethoxy 180 Me Pyridin-3-yl- S—(CH₂)₃— O 7-nitro 181 Me Phenyl S—CH₂—C(═CH₂)—CH₂ CH₂ 8-bromo 182 Me Tetrazolyl- S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy 183 Propyl 2-Aminothiazol-4yl- S—(CH₂)₃— CH₂ 7-carboxamido 184 Me 3-Br-Pyridin-5-yl- S—(CH₂)₃— CH₂ 8-fluoro 185 Me N-Methyl-2-Pyrrolyl- S—CH₂—CH═CH—CH₂— CH₂ 8-fluoro 186 Propyl 2-Thienyl COO—(CH₂)₄— CH₂ 6-methoxy 187 Me 2-Thienyl S—(CH₂)₃— CH₂ 6-methoxy 188 Propyl 3-cyano-phenyl CONH—(CH₂)₅— CH₂ 7-methyl 189 Propyl Pyridin-4-yl- S—(CH₂)₃— CH₂ 7-carboxamido 190 Me 3-Cyano-phenyl S—(CH₂)₃— CH₂ H 191 isoPropyl 4-Methoxyphenyl S—(CH₂)₃— O 7-sulfonamido 192 Me Phenyl S—(CH₂)₃— CH₂ 8-trifluoromethoxy 193 Me 2-Pyrazinyl- S—(CH₂)₃— CH₂ 7-sulfonamido 194 Ethyl Phenyl S—(CH₂)₃— CH₂ 7-nitro 195 Phenyl 3-Benzthienyl- S—(CH₂)₃— CH₂ H 196 Me 2-Pyrazinyl- S—(CH₂)₃— CH₂ 8-fluoro 197 Me 3-Jod-phenyl S—(CH₂)₃— CH₂ 7-cyano 198 Ethyl 4-Methylthiazol-5-yl S—CH₂—C(═CH₂)—CH₂ CH₂ 7-sulfonamido 199 Me 3-Cyano-phenyl S—(CH₂)₃— CH₂ 7-tert-butyl 200 cycPropyl 2-Me-4-Oxazolyl- S—(CH₂)₃— CH₂ 7-tert-butyl 201 Me 3-Jod-phenyl S—(CH₂)₃— CH₂ 6-methoxy 202 Me 2,5-Di-methyl-furanyl-3- S—(CH₂)₃— CH₂ 8-fluoro 203 Propyl 3-Jod-phenyl COO—(CH₂)₄— CH₂ 8-trifluoromethoxy 204 isoPropyl 4-Methoxyphenyl S—(CH₂)₃— CH₂ 7-sulfonamido 205 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— CH₂ 7-cyano 206 Ethyl Pyridin-3-yl- S—CH₂—C(CH₃)═CH—CH₂— O 7-tert-butyl 207 cycPropyl 3-Benzthienyl- S—(CH₂)₃— CH₂ 8-fluoro 208 Me Pyridin-3-yl- S—(CH₂)₃— CH₂ 7-sulfonamido 209 Phenyl 4-Imidazolyl- S—(CH₂)₃— CH₂ H 210 Propyl Phenyl S—(CH₂)₃— O 7-carboxamido 211 Me Phenyl S—(CH₂)₇— O 7-tert-butyl 212 Me 4-Methoxyphenyl S—(CH₂)₃— O 7-cyano 213 Me 3-Br-Pyridin-5-yl- S—(CH₂)₃— CH₂ 7-tert-butyl 214 Hexyl 4-Methoxyphenyl S—(CH₂)₃— CH₂ 6-methoxy 215 isoPropyl Methylamino S—(CH₂)₃— CH₂ 6-methoxy 216 Me 2,5-Di-methyl-furanyl-3- S—(CH₂)₃— CH₂ 6-methoxy 217 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— CH₂ 7-tert-butyl 218 Me Phenyl O—(CH₂)₃— CH₂ 7-sulfonamido 219 Me Pyridin-3-yl- S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy 220 Ethyl N-Methyl-2-Pyrrolyl- (CH₂)₄— O 9-methyl 221 isoPropyl Tetrazolyl- S—(CH₂)₃— CH₂ 6-methoxy 222 Me 4-Methylthiazol-5-yl S—(CH₂)₃— CH₂ 7-sulfonamido 223 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— O 7-cyano 224 Me 5-Methyl imidazol-4-yl- S—(CH₂)₃— CH₂ 7-tert-butyl 225 Me Phenyl S—(CH₂)₇— CH₂ 7-tert-butyl 226 Ethyl 2-Thienyl CO—(CH₂)₃— O H 227 Me Methylamino S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy 228 isoPropyl 3-Benzthienyl- S—(CH₂)₃— O 8-trifluoromethoxy 229 Me 4-Methylthiazol-5-yl S—(CH₂)₃— O 7-cyano 230 Propyl Phenyl S—(CH₂)₃— CH₂ 7-carboxamido 231 Me Phenyl S—(CH₂)₃— CH₂ H 232 isoPropyl Phenyl S—(CH₂)₃— CH₂ 7-sulfonamido 233 Me 3-Jod-phenyl O—(CH₂)₃— O 7-nitro 234 Me 4-Methylthiazol-5-yl S—(CH₂)₃— CH₂ 7-nitro 235 Me Phenyl S—(CH₂)₃— O 7-cyano 236 Me 2-Thienyl S—(CH₂)₃— CH₂ H 237 Et Amino S—(CH₂)₃— CH₂ 7-tert-butyl 238 Me 4-Methylthiazol-5-yl S—(CH₂)₃— CH₂ 6-methoxy 239 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— CH₂ 6-methoxy 240 cycPropyl Cyclohexyl- S—(CH₂)₃— CH₂ 7-tert-butyl 241 Ethyl Phenyl CO—(CH₂)₃— CH₂ H 242 Me Pyridin-3-yl- S—(CH₂)₃— CH₂ H 243 Me 4-Methoxyphenyl S—(CH₂)₃— O H 244 Me N-Propyl-tetrazolyl- S—(CH₂)₃— CH₂ H 245 Me 2-Pyrazinyl- S—(CH₂)₃— CH₂ H 246 Ethyl 4-Methylthiazol-5-yl S—CH₂—C(CH₃)═CH—CH₂— O 7-tert-butyl 247 Me 2-Thienyl S—(CH₂)₃— CH₂ 7-nitro 248 Me 4-Methylthiazol-5-yl S—(CH₂)₃— CH₂ 8-fluoro 249 Phenyl 3-Benzthienyl- S—(CH₂)₃— O H 250 Me 3-Jod-phenyl S—(CH₂)₃— O 7-tert-butyl 251 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— CH₂ 8-fluoro 252 Et Pyridin-4-yl- S—(CH₂)₃— CH₂ 7-tert-butyl 253 Phenyl Carboxamido S—(CH₂)₃— CH₂ 8-fluoro 254 Ethyl Phenyl S—(CH₂)₃— O 7-nitro 255 Me 3-Pyrrolyl S—(CH₂)₃— CH₂ 7-carboxamido 256 isoPropyl 3-Pyrrolyl S—(CH₂)₃— O 8-trifluoromethoxy 257 Me Amino S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy 258 Propyl Phenyl COO—(CH₂)₄— O 7-methyl 259 Me Oxadiazol-2-yl S—(CH₂)₃— O 7-methoxy 8-methoxy 260 Me 2-Aminothiazol-4yl- S—(CH₂)₃— CH₂ 8-fluoro 261 Phenyl Amino S—(CH₂)₃— CH₂ H 262 Me Phenyl S—(CH₂)₁₀— O 7-methyl 263 Me Phenyl S—(CH₂)₃— CH₂ 8-fluoro 264 Me Pyridin-4-yl- S—(CH₂)₃— CH₂ H 265 Ethyl 4-Methylthiazol-5-yl S—(CH₂)₆— O 7-cyano 266 Hexyl Pyridin-4-yl- S—(CH₂)₃— CH₂ 6-methoxy 267 Me 5-Methyl imidazol-4-yl- S—(CH₂)₃— O H 268 butyl Cyano S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy 269 Me 4-Methylthiazol-5-yl S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy 270 Me 2-Pyrazinyl- (CH₂)₄— CH₂ 7-methyl 271 Me 4-Methylthiazol-5-yl S—(CH₂)₃— CH₂ H 272 Me Cyclohexyl- S—(CH₂)₃— CH₂ 6-methoxy 273 Me 4-Methoxyphenyl S—(CH₂)₃— O 7-methoxy 8-methoxy 274 Me 2-Thienyl S—(CH₂)₇— O 8-trifluoromethoxy 275 Phenyl Cyano S—(CH₂)₃— O H 276 Me Pyridin-3-yl- S—(CH₂)₃— CH₂ 7-cyano 277 Me Phenyl (CH₂)₄— CH₂ H 278 butyl 3-Pyrrolyl S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy 279 Me Phenyl S—(CH₂)₇— O 7-tert-butyl 280 Me 4-Methylthiazol-5-yl S—(CH₂)₃— CH₂ 7-cyano 281 Me 2-Thienyl S—CH₂—C(═CH₂)—CH₂ O 8-fluoro 282 Me 4-Methoxyphenyl S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy 283 Me 5-Methyl imidazol-4-yl- S—(CH₂)₃— CH₂ H 284 Me 4-Methylthiazol-5-yl S—(CH₂)₃— O 7-cyano 285 Me 2-Pyrazinyl- S—(CH₂)₃— CH₂ 7-cyano 286 Me 3-Jod-phenyl S—(CH₂)₃— O 7-nitro 287 Me 2-Thienyl S—(CH₂)₈— CH₂ 6-methoxy 288 isoPropyl Oxadiazol-2-yl S—(CH₂)₃— CH₂ 6-methoxy 289 Me 3-Br-Pyridin-5-yl- S—(CH₂)₃— CH₂ 6-methoxy 290 Me Pyridin-3-yl- S—(CH₂)₃— CH₂ 7-nitro 291 Me 4-Methoxyphenyl S—(CH₂)₃— CH₂ H 292 Ethyl 4-Methylthiazol-5-yl S—(CH₂)₆— CH₂ 7-cyano 293 Me 2-Pyrazinyl- S—(CH₂)₃— CH₂ 7-methoxy 8-methoxy 294 Me 3-Pyrrolyl S—(CH₂)₃— CH₂ H 295 Me 4-Methoxyphenyl O—(CH₂)₃— CH₂ H 296 Me 3-Jod-phenyl S—(CH₂)₃— O 7-cyano 297 Ethyl Pyridin-3-yl- S—CH₂—C(CH₃)═CH—CH₂— CH₂ 7-tert-butyl *If no meaning is given, R⁷ is hydrogen.

Here and in the following tables is:

Me=methyl

Et=ethyl

cycPropyl=cyclopropyl

The following compounds can be prepared in an analogous way in principles:

TABLE 2

Ex. R¹ R² A Y R⁶ R⁷* 298 Me N-Methyl-2-Pyrrolyl- (CH₂)₄— CH₂ 10-methyl 299 Ethyl 2-Aminothiazol-4yl- S—(CH₂)₃— O H 300 Me 3-Jod-phenyl S—(CH₂)₃— O 8-nitro 301 Me Amino S—(CH₂)₃— CH₂ 8-tert-butyl 302 Me 5-Methyl imidazol-4-yl- S—(CH₂)₃— CH₂ H 303 Me Cyclohexyl- S—(CH₂)₃— CH₂ 8-tert-butyl 304 Me 4-Methoxyphenyl S—(CH₂)₃— O H 305 Ethyl Pyridin-3-yl- S—(CH₂)₆— O 8-tert-butyl 306 Me 3-Jod-phenyl (CH₂)₄— O 8-tert-butyl 307 Me 5-Methyl imidazol-4-yl- S—(CH₂)₃— CH₂ 8-tert-butyl 308 Me 2-Thienyl (CH₂)₄— O H 309 Me 2-Me-4-Oxazolyl- S—(CH₂)₃— CH₂ 9-methyl 310 Me 2,5-Di-methyl-furanyl-3- S—(CH₂)₃— CH₂ 7-methoxy 311 Me 4-Methylthiazol-5-yl S—(CH₂)₃— O 8-cyano 312 Propyl 4-Methoxyphenyl COO—(CH₂)₃— CH₂ 8-sulfonamido 313 Propyl N-Methyl-2-Pyrrolyl- CONH—(CH₂)₄— CH₂ 9-trifluoromethoxy 314 Me 2-Thienyl S—(CH₂)₇— CH₂ 9-trifluoromethoxy 315 Me Pyridin-3-yl- S—(CH₂)₃— CH₂ 9-methyl 316 Me N-Propyl-tetrazolyl- S—(CH₂)₃— CH₂ 9-trifluoromethoxy 317 Me 3-Br-Pyridin-5-yl- S—(CH₂)₃— CH₂ 8-tert-butyl 318 Me 3-Cyano-phenyl S—(CH₂)₃— CH₂ 7-methoxy 319 Phenyl Amino S—(CH₂)₃— O H 320 Butyl 2,5-Di-methyl-furanyl-3- S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 321 Phenyl 3-Benzthienyl- S—(CH₂)₃— O H 322 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— CH₂ 8-tert-butyl 323 Propyl 3-cyano-phenyl CONH—(CH₂)₅— CH₂ 8-methyl 324 Me 3-Jod-phenyl S—(CH₂)₃— CH₂ 8-sulfonamido 325 Me Phenyl O—(CH₂)₃— CH₂ 8-sulfonamido 326 Me 4-Methylthiazol-5-yl (CH₂)₄— CH₂ 10-methyl 327 Me 3-Pyrrolyl S—(CH₂)₃— CH₂ 7-methoxy 328 Butyl 3-Cyano-phenyl S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 329 Ethyl 4-Methylthiazol-5-yl S—(CH₂)₆— O 8-cyano 330 Me Pyridin-4-yl- S—(CH₂)₃— O H 331 Butyl 2-Aminothiazol-4yl- S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 332 Propyl 4-Imidazolyl- S—(CH₂)₃— CH₂ 8-carboxamido 333 isoPropyl Tetrazolyl- S—(CH₂)₃— CH₂ 7-methoxy 334 Me Pyridin-3-yl- S—(CH₂)₃— O 8-cyano 335 Me N-Methyl-2-Pyrrolyl S—(CH₂)₃— O 8-nitro 336 Et Amino S—(CH₂)₃— CH₂ H 337 Phenyl Methylamino S—(CH₂)₃— CH₂ 9-methyl 338 Me 4-Methylthiazol-5-yl (CH₂)₄— O 10-methyl 339 Me 4-Methylthiazol-5-yl S—(CH₂)₃— CH₂ 8-sulfonamido 340 Me Methylamino S—(CH₂)₃— CH₂ 8-tert-butyl 341 Et 3-Cyano-phenyl S—(CH₂)₃— CH₂ H 342 Me 4-Methylthiazol-5-yl S—(CH₂)₃— O 8-nitro 343 Me 3-Jod-phenyl (CH₂)₄— CH₂ 8-tert-butyl 344 Me 4-Methylthiazol-5-yl S—(CH₂)₃— CH₂ H 345 Me 3-Br-Pyridin-5-yl- S—(CH₂)₃— CH₂ H 346 Propyl Pyridin-4-yl- S—(CH₂)₃— CH₂ 8-carboxamido 347 Me 4-Methoxyphenyl S—(CH₂)₃— CH₂ 8-cyano 348 isoPropyl 3-Benzthienyl- S—(CH₂)₃— CH₂ 9-trifluoromethoxy 349 Butyl 3-Benzthienyl- S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 350 Ethyl Pyridin-3-yl- (CH₂)₄— O H 351 Propyl 2-Aminothiazol-4yl- S—(CH₂)₃— CH₂ 8-carboxamido 352 Me Cyclohexyl- S—(CH₂)₃— CH₂ 9-methyl 353 Ethyl Phenyl S—(CH₂)₃— O 8-nitro 354 Me 4-Methoxyphenyl S—(CH₂)₃— O 8-methoxy 9-methoxy 355 Propyl Phenyl COO—(CH₂)₄— O 8-methyl 356 Me 2,5-Di-methyl-furanyl-3- S—(CH₂)₃— CH₂ 9-methyl 357 Me 3-Jod-phenyl S—(CH₂)₃— CH₂ H 358 Me Phenyl S—(CH₂)₃— CH₂ H 359 isoPropyl Oxadiazol-2-yl S—(CH₂)₃— CH₂ 7-methoxy 360 Me Phenyl S—(CH₂)₇— O 8-tert-butyl 361 Propyl 2-Pyrazinyl- COO—(CH₂)₄— CH₂ 9-trifluoromethoxy 362 Me 3-Pyrrolyl S—(CH₂)₃— CH₂ 8-carboxamido 363 Propyl Phenyl S—(CH₂)₃— CH₂ 8-carboxamido 364 Me 2-Pyrazinyl- O—(CH₂)₃— CH₂ H 365 Me Phenyl S—(CH₂)₇— O 8-tert-butyl 366 Me Pyridin-3-yl- S—(CH₂)₃— CH₂ 8-sulfonamido 367 Me 3-Jod-phenyl S—(CH₂)₃— CH₂ 8-cyano 368 Me 2-Thienyl S—(CH₂)₃— CH₂ 9-methyl 369 isoPropyl Methylamino S—(CH₂)₃— CH₂ 7-methoxy 370 Ethyl 3-Jod-phenyl S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 371 Ethyl Phenyl CO—(CH₂)₃— O H 372 Phenyl 4-Imidazolyl- S—(CH₂)₃— O H 373 Ethyl 4-Methylthiazol-5-yl S—(CH₂)₆— CH₂ 8-cyano 374 Me 3-Jod-phenyl S—(CH₂)₃— CH₂ 7-methoxy 375 Hexyl 4-Imidazolyl- S—(CH₂)₃— CH₂ 7-methoxy 376 Me Phenyl S—(CH₂)₃— CH₂ 9-trifluoromethoxy 377 Me 3-Jod-phenyl O—(CH₂)₃— O 8-nitro 378 Me 5-Methyl imidazol-4-yl- S—(CH₂)₃— CH₂ 7-methoxy 379 Ethyl Pyridin-3-yl- S—CH₂—C(CH₃)═CH—CH₂— O 8-tert-butyl 380 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— CH₂ 7-methoxy 381 Ethyl Phenyl S—CH₂—C(CH₃)═CH—CH₂— CH₂ 8-tert-butyl 382 Me Pyridin-3-yl- S—(CH₂)₈— O 9-trifluoromethoxy 383 Me 2-Thienyl S—(CH₂)₃— O 8-nitro 384 Me 2-Pyrazinyl- (CH₂)₄— O 8-methyl 385 Butyl 3-Br-Pyridin-5-yl- S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 386 Me 2-Pyrazinyl- S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 387 Me Phenyl S—(CH₂)₃— O 8-cyano 388 Me 4-Methoxyphenyl S—(CH₂)₃— O 8-nitro 389 Me Cyclohexyl- S—(CH₂)₃— CH₂ 7-methoxy 390 Me Phenyl CO—CH₂—C(═CH₂)—CH₂ O 8-tert-butyl 391 Me N-Methyl-2-Pyrrolyl- (CH₂)₄— O 10-methyl 392 Me Oxadiazol-2-yl S—(CH₂)₃— CH₂ 9-methyl 393 Me 2-Pyrazinyl- S—(CH₂)₃— CH₂ H 394 Ethyl Phenyl S—(CH₂)₃— CH₂ 8-nitro 395 Me Pyridin-3-yl- S—(CH₂)₃— CH₂ 8-nitro 396 Me 2-Me-4-Oxazolyl- S—(CH₂)₃— CH₂ 7-methoxy 397 Me Pyridin-3-yl S—(CH₂)₃— CH₂ 8-tert-butyl 398 Ethyl Phenyl CO—(CH₂)₃— CH₂ H 399 Me 3-Cyano-phenyl S—(CH₂)₃— O H 400 Me Pyridin-3-yl- (CH₂)₄— O H 401 Me 4-Jod-phenyl S—(CH₂)₃— CH₂ 8-tert-butyl 402 Butyl 3-Pyrrolyl S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 403 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— O 8-cyano 404 Me 2-Me-4-Oxazolyl- S—(CH₂)₃— CH₂ 8-tert-butyl 405 isoButyl Methylamino S—(CH₂)₃— O H 406 Me 2-Thienyl S—(CH₂)₃— O 8-nitro 407 Me 2-Thienyl S—(CH₂)₇— O 9-trifluoromethoxy 408 Me 4-Methylthiazol-5-yl S—(CH₂)₃— O 8-cyano 409 Me 2-Me-4-Oxazolyl- S—(CH₂)₃— O 8-tert-butyl 410 Me 2-Thienyl S—CH₂—C(═CH₂)—CH₂ CH₂ 9-fluoro 411 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— O 8-cyano 412 Me Phenyl S—(CH₂)₃— CH₂ 9-methyl 413 Me 3-Jod-phenyl S—(CH₂)₃— CH₂ 9-methyl 414 Me Pyridin-3-yl- S—(CH₂)₃— O 8-tert-butyl 415 Ethyl 2-Thienyl (CH₂)₄— O H 416 Me Tetrazolyl- S—(CH₂)₃— CH₂ 9-methyl 417 Me 2-Thienyl S—(CH₂)₈— CH₂ 7-methoxy 418 Me Pyridin-4-yl- S—(CH₂)₃— CH₂ 9-trifluoromethoxy 419 Me Phenyl S—CH₂—C(═CH₂)—CH₂ CH₂ 9-bromo 420 Me Phenyl S—(CH₂)₁₀— O 8-methyl 421 Me Oxadiazol-2-yl S—(CH₂)₃— CH₂ H 422 Me Oxadiazol-2-yl S—(CH₂)₃— O 8-methoxy 9-methoxy 423 Butyl 4-Imidazolyl- S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 424 isoPropyl 3-Pyrrolyl S—(CH₂)₃— O 9-trifluoromethoxy 425 isoPropyl 3-Cyano-phenyl S—(CH₂)₃— CH₂ 9-trifluoromethoxy 426 Butyl N-Propyl-tetrazolyl- S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 427 Me Pyridin-3-yl- S—(CH₂)₈— CH₂ 9-trifluoromethoxy 428 cycPropyl 4-Methoxyphenyl S—(CH₂)₃— CH₂ 9-methyl 429 Me Phenyl CO—CH₂—C(═CH₂)—CH₂ CH₂ 8-tert-butyl 430 Me 3-Br-Pyridin-5-yl- S—(CH₂)₃— CH₂ 9-methyl 431 Me 2-Pyrazinyl- (CH₂)₄— CH₂ 8-methyl 432 Me Phenyl CO—CH₂—C(═CH₂)—CH₂ O 8-tert-butyl 433 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— CH₂ 8-cyano 434 Me 2-Thienyl S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 435 Ethyl Pyridin-3-yl- S—CH₂—C(CH₃)═CH—CH₂— CH₂ 8-tert-butyl 436 Me Methylamino S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 437 Me 2-Me-4-Oxazolyl- S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 438 isoPropyl Phenyl S—(CH₂)₃— O 8-sulfonamido 439 Ethyl Phenyl S—CH₂—C(CH₃)═CH—CH₂— O 8-tert-butyl 440 Me 3-Br-Pyridin-5-yl- S—(CH₂)₃— CH₂ 7-methoxy 441 Me Cyano S—(CH₂)₃— CH₂ H 442 Me 3-Br-Pyridin-5-yl- S—(CH₂)₃— O H 443 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— CH₂ 8-nitro 444 Me N-Propyl-tetrazolyl- S—(CH₂)₃— CH₂ 8-tert-butyl 445 Me 4-Methoxyphenyl S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 446 Me 2-Pyrazinyl- S—(CH₂)₃— CH₂ 8-sulfonamido 447 Me Phenyl S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 448 Me 4-Methoxyphenyl (CH₂)₄— CH₂ 10-fluoro 449 Me 2-Thienyl S—(CH₂)₃— CH₂ 8-sulfonamido 450 isoPropyl 5-Methyl imidazol-4-yl- S—(CH₂)₃— CH₂ 9-trifluoromethoxy 451 Ethyl 3-Jod-phenyl (CH₂)₄— O 8-tert-butyl 452 Me 2-Pyrazinyl- S—(CH₂)₃— CH₂ 8-cyano 453 isoPropyl 2-Aminothiazol-4yl- S—(CH₂)₃— CH₂ 9-trifuormethoxy 454 cycPropyl 3-Cyano-phenyl S—(CH₂)₃— CH₂ 9-methyl 455 isoPropyl 3-Pyrrolyl S—(CH₂)₃— CH₂ 9-trifluoromethoxy 456 Me 2-Aminothiazol-4yl- S—(CH₂)₃— CH₂ 7-methoxy 457 Me Pyridin-3-yl- S—(CH₂)₃— CH₂ 7-methoxy 458 Me 2-Aminothiazol-4yl- S—(CH₂)₃— CH₂ H 459 Me Phenyl O—(CH₂)₄— O 9-iod 460 Me 2-Thienyl S—(CH₂)₃— O 8-cyano 461 Ethyl Pyridin-3-yl- S—CH₂—CH═CH—CH₂— O 9-fluoro 462 Propyl 4-Methylthiazol-5-yl CONH—(CH₂)₄— CH₂ 8-methyl 463 Phenyl 4-Imidazolyl- S—(CH₂)₃— CH₂ H 464 Hexyl 3-Benzthienyl- S—(CH₂)₃— CH₂ 7-methoxy 465 Ethyl Pyridin-3-yl- S—(CH₂)₆— CH₂ 8-tert-butyl 466 Me 3-Pyrrolyl S—(CH₂)₃— O H 467 cycPropyl 2-Thienyl S—(CH₂)₃— CH₂ H 468 Ethyl Phenyl S—CH₂—C(CH₃)═CH—CH₂— O 8-sulfonamido 469 Me 2-Aminothiazol-4yl- S—(CH₂)₃— CH₂ 8-tert-butyl 470 isoPropyl 3-Benzthienyl- S—(CH₂)₃— O 9-trifuormethoxy 471 Me Pyridin-3-yl- S—(CH₂)₃— O 8-nitro 472 Ethyl 2-Thienyl CO—(CH₂)₃— CH₂ H 473 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— CH₂ H 474 Propyl Phenyl CONH—(CH₂)₅— O 8-methyl 475 isoPropyl 5-Methyl imidazol-4-yl- S—(CH₂)₃— O 9-trifluoromethoxy 476 Me 4-Methoxyphenyl S—(CH₂)₃— CH₂ 8-tert-butyl 477 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 478 cycPropyl N-Propyl-tetrazolyl- S—(CH₂)₃— CH₂ 9-methyl 479 Et 2,5-Di-methyl-furanyl-3- S—(CH₂)₃— CH₂ H 480 isoButyl Oxadiazol-2-yl S—(CH₂)₃— O 8-tert-butyl 481 Hexyl N-Propyl-tetrazolyl- S—(CH₂)₃— CH₂ 7-methoxy 482 Propyl 2-Thienyl COO—(CH₂)₄— CH₂ 7-methoxy 483 Phenyl Cyano S—(CH₂)₃— O H 484 Me 2-Thienyl S—CH₂—C(═CH₂)—CH₂ O 9-fluoro 485 Me Pyridin-4-yl- S—(CH₂)₃— CH₂ 8-tert-butyl 486 Me 2-Pyrazinyl- S—(CH₂)₃— O 8-cyano 487 Butyl 5-Methyl imidazol-4-yl- S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 488 Ethyl 2-Thienyl CO—(CH₂)₃— O H 489 Me Oxadiazol-2-yl S—(CH₂)₃— CH₂ 8-tert-butyl 490 isoPropyl Cyano S—(CH₂)₃— CH₂ 7-methoxy 491 Me Amino S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 492 Me N-Methyl-2-Pyrrolyl- S—CH₂—CH═CH—CH₂— CH₂ 9-fluoro 493 Me Phenyl S—(CH₂)₇— CH₂ 8-tert-butyl 494 Me 2-Pyrazinyl- O—(CH₂)₃— O H 495 Me Phenyl S—(CH₂)₁₀— CH₂ 8-methyl 496 Butyl Pyridin-4-yl- S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 497 Ethyl 4-Methylthiazol-5-yl S—(CH₂)₆— O 8-cyano 498 Me 4-Methoxyphenyl S—(CH₂)₃— O 8-cyano 499 Me 3-Pyrrolyl S—(CH₂)₃— CH₂ 9-methyl 500 isoPropyl Phenyl S—(CH₂)₃— CH₂ 8-sulfonamido 501 Me Tetrazolyl- S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 502 Phenyl 2-Pyrazinyl- S—(CH₂)₃— CH₂ 8-tert-butyl 503 isoPropyl 4-Methoxyphenyl S—(CH₂)₃— CH₂ 8-sulfonamido 504 Phenyl Carboxamido S—(CH₂)₃— CH₂ 9-methyl 505 Me 4-Methylthiazol-5-yl S—(CH₂)₃— O H 506 Me 3-Cyano-phenyl S—(CH₂)₃— CH₂ 8-tert-butyl 507 Pentyl Phenyl CH₂—CH₂—CH═CH—CH₂— O H 508 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— CH₂ 9-methyl 509 Me Pyridin-3-yl- S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 510 Me 4-Methoxyphenyl O—(CH₂)₃— CH₂ H 511 Me 2-Pyrazinyl- S—(CH₂)₃— CH₂ 9-methyl 512 Phenyl 3-Benzthienyl- S—(CH₂)₃— CH₂ 8-tert-butyl 513 Me Phenyl O—(CH₂)₄— CH₂ 8-tert-butyl 514 Me 3-Jod-phenyl O—(CH₂)₃— O H 515 Me 3-Thienyl S—(CH₂)₃— CH₂ 8-tert-butyl 516 cycPropyl Pyridin-3-yl- S—(CH₂)₃— CH₂ H 517 Me Pyridin-3-yl- S—(CH₂)₃— CH₂ 8-cyano 518 Me 4-Methylthiazol-5-yl S—(CH₂)₃— CH₂ 8-nitro 519 Me Phenyl S—CH₂—C(═CH₂)—CH₂ O 9-bromo 520 Me Pyridin-3-yl- (CH₂)₄— CH₂ H 521 Me 2-Thienyl S—(CH₂)₃— CH₂ 7-methoxy 522 Propyl Phenyl CONH—(CH₂)₅— CH₂ 8-methyl 523 Me N-Propyl-tetrazolyl- S—(CH₂)₃— O H 524 Ethyl Phenyl S—(CH₂)₃— O 8-nitro 525 Me Phenyl (CH₂)₄— CH₂ H 526 Propyl 3-Cyano-phenyl S—(CH₂)₃— CH₂ 8-carboxamido 527 Me Oxadiazol-2-yl S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 528 Me 4-Methoxyphenyl S—(CH₂)₃— CH₂ 8-nitro 529 Me Phenyl (CH₂)₄— O H 530 isoPropyl 3-Br-Pyridin-5-yl- S—(CH₂)₃— CH₂ 9-trifluoromethoxy 531 Ethyl 4-Methylthiazol-5-yl S—CH₂—C(═CH₂)—CH₂ CH₂ 8-sulfonamido 532 Me Tetrazolyl- S—(CH₂)₃— CH₂ H 533 Me 4-Methylthiazol-5-yl S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 534 Propyl Phenyl COO—(CH₂)₄— CH₂ 8-methyl 535 Propyl 3-Br-Pyridin-5-yl- S—(CH₂)₃— CH₂ 8-carboxamido 536 Me 2-Pyrazinyl- S—(CH₂)₃— O H 537 Me 2-Thienyl S—(CH₂)8— O 7-methoxy 538 Me 3-Jod-phenyl O—(CH₂)₃— CH₂ H 539 Me Phenyl S—(CH₂)₃— O H 540 Hexyl Pyridin-4-yl- S—(CH₂)₃— CH₂ 7-methoxy 541 Me 2-Thienyl (CH₂)₄— CH₂ H 542 cycPropyl Pyridin-4-yl- S—(CH₂)₃— CH₂ 9-methyl 543 cycPropyl Amino S—(CH₂)₃— CH₂ 9-methyl 544 Me 3-Jod-phenyl S—(CH₂)₃— O 8-tert-butyl 545 Ethyl 4-Methylthiazol-5-yl S—CH₂—C(CH₃)═CH—CH₂— CH₂ 8-tert-butyl 546 Me 3-Pyrrolyl S—(CH₂)₃— CH₂ H 547 Propyl Phenyl S—(CH₂)₃— O 8-carboxamido 548 Me 4-Imidazolyl- S—(CH₂)₃— CH₂ 8-tert-butyl 549 Propyl Pyridin-3-yl- CONH—(CH₂)₄— CH₂ 8-methyl 550 isoPropyl 4-Methoxyphenyl S—(CH₂)₃— O 8-sulfonamido 551 Me 2-Me-4-Oxazolyl- S—(CH₂)₃— CH₂ H 552 Me 3-Jod-phenyl S—(CH₂)₃— O 8-cyano 553 Me 2-Thienyl S—(CH₂)₃— O H 554 cycPropyl 3-Benzthienyl- S—(CH₂)₃— CH₂ 9-methyl 555 Me 4-Methylthiazol-5-yl S—(CH₂)₃— CH₂ 9-methyl 556 Hexyl Amino S—(CH₂)₃— CH₂ 7-methoxy 557 isoButyl Tetrazolyl- S—(CH₂)₃— O H 558 Et 4-Methoxyphenyl S—(CH₂)₃— CH₂ H 559 cycPropyl 4-Imidazolyl- S—(CH₂)₃— CH₂ 9-methyl 560 Me Phenyl S—(CH₂)₃— CH₂ 8-cyano 561 Me 2-Thienyl O—(CH₂)₄— CH₂ 8-tert-butyl 562 Me 2-Aminothiazol-4yl- S—(CH₂)₃— CH₂ 9-methyl 563 Butyl Cyano S—(CH₂)₃— CH₂ 8-methoxy 9-methoxy 564 Me 5-Methyl imidazol-4-yl- S—(CH₂)₃— CH₂ 9-methyl 565 Me Phenyl S—(CH₂)₃— CH₂ 7-methoxy 566 Me 2-Pyrazinyl- S—(CH₂)₃— CH₂ 8-nitro 567 Phenyl 3-Benzthienyl- S—(CH₂)₃— CH₂ H 568 Me 2,5-Di-methyl-furanyl-3- S—(CH₂)₃— O H 569 Et Pyridin-4-yl- S—(CH₂)₃— CH₂ H 570 Me Tetrazolyl- S—(CH₂)₃— CH₂ 8-tert-butyl 571 Me 2-Thienyl S—(CH₂)₃— CH₂ 8-cyano 572 Me 4-Methylthiazol-5-yl S—(CH₂)₃— CH₂ 8-cyano 573 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— CH₂ 8-sulfonamido 574 Hexyl 4-Methoxyphenyl S—(CH₂)₃— CH₂ 7-methoxy 575 Me 2-Pyrazinyl- S—(CH₂)₃— O 8-nitro 576 Et N-Propyl-tetrazolyl- S—(CH₂)₃— CH₂ H 577 Me 3-Pyrrolyl S—(CH₂)₃— CH₂ 8-tert-butyl 578 Me 2-Pyrazinyl- S—(CH₂)₃— CH₂ 7-methoxy 579 Me 4-Methoxyphenyl (CH₂)₄— O 10-fluoro 580 Ethyl Pyridin-3-yl S—CH₂—CH═CH—CH₂— CH₂ 9-fluoro 581 Ethyl N-Methyl-2-Pyrrolyl- (CH₂)₄— O 10-methyl 582 Me 5-Methyl imidazol-4-yl- S—(CH₂)₃— O H 583 Ethyl 4-Methylthiazol-5-yl S—CH₂—C(═CH₂)—CH₂ O 8-sulfonamido 584 Me 2,5-Di-methyl-furanyl-3- S—(CH₂)₃— CH₂ 8-tert-butyl H 585 Me 3-Jod-phenyl S—(CH₂)₃— CH₂ 8-nitro 586 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— O H 587 Me 2-Thienyl S—(CH₂)₃— CH₂ 8-nitro 588 cycPropyl Methylamino S—(CH₂)₃— CH₂ H 589 Me 4-Methylthiazol-5-yl S—(CH₂)₃— CH₂ 7-methoxy 590 Ethyl 4-Methylthiazol-5-yl S—CH₂—C(CH₃)═CH—CH₂— O 8-tert-butyl 591 Propyl 3-Jod-phenyl COO—(CH₂)₄— CH₂ 9-trifluoromethoxy *If no meaning is given, R⁷ is hydrogen.

The following compounds can be prepared in an analogous way in principles:

TABLE 3

Ex. R¹ R² A R⁶ 592 Me Tetrazolyl- S—(CH₂)₃— 7-tert-butyl 593 Me 3-Jod-phenyl O—(CH₂)₃— 7-nitro 594 Me 4-Methoxyphenyl S—CH₂—CH═CH—CH₂— 6-methoxy 595 Me Amino S—CH₂—C(CH₃)═CH—CH₂— 7-tert-butyl 596 Me Methylamino S—(CH₂)₃— 7-tert-butyl 597 Propyl 4-Methoxyphenyl S—(CH₂)₃— 7-nitro 598 Me 3-Pyrrolyl S—(CH₂)₃— 7-tert-butyl 599 Me 3-Jod-phenyl S—(CH₂)₄— 6-methoxy 600 Me 2-Pyrazinyl- S—(CH₂)₃— 7-nitro 601 isoPropyl 2-Thienyl CONH—(CH₂)₄— H 602 Me 4-Methylthiazol-5-yl S—(CH₂)₃— 6-chloroo 603 Me 2-Pyrazinyl- S—(CH₂)₃— 6-chloroo 604 Butyl Oxadiazol-2-yl S—(CH₂)₃— 7-tert-butyl 605 cycPropyl Phenyl (CH₂)₄— 6-methyl 606 Me 4-Imidazolyl- S—(CH₂)₃— 7-tert-butyl 607 Phenyl 3-Benzthienyl- S—(CH₂)₃— 7-tert-butyl 608 Propyl 2-Thienyl S—CH₂—CH═CH—CH₂— 6-methoxy 609 Hexyl Phenyl (CH₂)₄— 6-methyl 610 Propyl Phenyl S—CH₂—C(CH₃)═CH—CH₂— 6-methyl 611 isoPropyl Phenyl S—CH₂—C(═CH₂)—CH₂ 6-methyl 612 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— 6-methoxy 613 Me 4-Jod-phenyl S—CH₂—CH═CH—CH₂— 7-tert-butyl 614 Me Pyridin-3-yl- S—CH₂—CH═CH—CH₂— 7-tert-butyl 615 Propyl Phenyl S—(CH₂)₃— 6-methoxy 616 Me 3-Jod-phenyl S—(CH₂)₃— 6-chloroo 617 Me 3-Thienyl S—(CH₂)₃— 7-tert-butyl 618 Ethyl Phenyl (CH₂)₈— H 619 Me Cyclohexyl- S—(CH₂)₃— 7-tert-butyl 620 Me Pyridin-3-yl- S—(CH₂)₃— H 621 Me Phenyl S—(CH₂)3— 7-cyano 622 Ethyl Phenyl S—(CH₂)₃— 6-methyl 623 Me Pyridin-4-yl- O—(CH₂)₃— 7-tert-butyl 624 Ethyl 4-Methylthiazol-5-yl S—CH₂—C(CH₃)═CH—CH₂— 7-cyano 625 Me 2-Pyrazinyl- S—(CH₂)₃— 6-methoxy 626 Ethyl Phenyl S—(CH₂)₃— 6-chloroo 627 Ethyl 3-Jod-phenyl S—CH₂—C(CH₃)═CH—CH₂— 7-cyano 628 Me 2-Thienyl S—(CH₂)₃— 7-nitro 629 Ethyl Pyridin-3-yl- S—(CH₂)₃— 7-cyano 630 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— 6-chloroo 631 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— 7-tert-butyl 632 isoPropyl 4-Methoxyphenyl S—(CH₂)₃— 7-tert-butyl 633 Me 3-Br-Pyridin-5-yl- S—CH₂—C(CH₃)═CH—CH₂— 7-tert-butyl 634 isoPropyl 3-Cyano-phenyl O—(CH₂)₈— 7-tert-butyl 635 Ethyl Phenyl S—(CH₂)₃— 7-nitro 636 Me 5-Methyl imidazol-4-yl- S—(CH₂)₃— 7-tert-butyl 637 Ethyl N-Methyl-2-Pyrrolyl- S—(CH₂)₃— 7-cyano 638 Me Pyridin-3-yl- S—(CH₂)₃— 6-chloroo 639 Me 4-Methylthiazol-5-yl S—(CH₂)₃— 6-methoxy 640 Phenyl 2-Pyrazinyl- S—CH₂—C(CH₃)═CH—CH₂— 7-tert-butyl 641 Hexyl Phenyl (CH₂)₄— 6-methyl 642 Me 4-Methoxyphenyl S—(CH₂)₃— 6-chloroo 643 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— 7-nitro 644 Me 2,5-Di-methyl-furanyl-3- S—(CH₂)₃— 7-tert-butyl 645 Propyl Phenyl COO—(CH₂)₄— H 646 cycPropyl Phenyl O—(CH₂)₃— 6-methyl 647 Me 2-Thienyl S—(CH₂)₇— 6-chloro 648 isoPropyl 2-Aminothiazol-4y1- S—(CH₂)₃— 7-tert-butyl 649 Butyl Phenyl (CH₂)₄— 6-methyl 650 Me 2-Pyrazinyl- S—(CH₂)₃— 7-cyano 651 Me 4-Methoxyphenyl S—CH₂—CH═CH—CH2— H 652 Me N-Propyl-tetrazolyl- S—(CH₂)₃— 7-tert-butyl 653 Me Pyridin-3-yl- S—(CH₂)₃— 6-methoxy 654 Butyl Phenyl CO—(CH₂)₃— 6-methyl 655 Me 2-Me-4-Oxazolyl- S—CH₂—CH═CH—CH₂— 7-tert-butyl 656 Me 4-Methylthiazol-5-yl S—(CH₂)₉— 7-nitro 657 Me 2-Thienyl S—(CH₂)₃— 7-cyano

The following compounds can be prepared in an analogous way in principles:

TABLE 4

Ex. R¹ R² A R⁶ 658 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— 7-methoxy 659 Me 2-Pyrazinyl- S—(CH₂)₃— 7-methoxy 660 Me Amino S—CH₂—C(CH₃)═CH—CH₂— 8-tert-butyl 661 Me 4-Methylthiazol-5-yl S—(CH₂)₉— 8-nitro 662 Me 4-Imidazolyl- S—(CH₂)₃— 8-tert-butyl 663 Ethyl Pyridin-3-yl- S—(CH₂)₃— 8-cyano 664 Me Pyridin-3-yl- S—(CH₂)₃— 7-chloro 665 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— H 666 Ethyl Phenyl (CH₂)₈— H 667 Me 3-Jod-phenyl O—(CH₂)₃— 8-nitro 668 Ethyl Phenyl S—(CH₂)₃— 7-methyl 669 Me Pyridin-4-yl- S—CH₂—C(CH₃)═CH—CH₂— 8-tert-butyl 670 Me 4-Methoxyphenyl S—CH₂—CH═CH—CH₂— 7-methoxy 671 Me Pyridin-3-yl- S—CH₂—CH═CH—CH₂— 8-tert-butyl 672 Propyl 4-Methoxyphenyl S—(CH₂)₃— 8-nitro 673 Me 3-Pyrrolyl S—(CH₂)₃— 8-tert-butyl 674 Propyl 2-Thienyl S—CH₂—CH═CH—CH₂— 7-methoxy 675 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— 8-nitro 676 Butyl Phenyl CO—(CH₂)₃— 7-methyl 677 Me 2-Aminothiazol-4y1- S—(CH₂)₃— 8-tert-butyl 678 Me Pyridin-3-yl- S—(CH₂)₃— H 679 Ethyl N-Methyl-2-Pyrrolyl- S—(CH₂)₃— 8-cyano 680 Me 2-Thienyl S—(CH₂)₃— 8-cyano 681 isoPropyl 5-Methyl imidazol-4-yl- S—(CH₂)₃— 8-tert-butyl 682 Butyl Oxadiazol-2-yl S—CH₂—C(CH₃)═CH—CH₂— 8-tert-butyl 683 Me 4-Methylthiazol-5-yl S—(CH₂)₃— H 684 Hexyl Phenyl (CH₂)₄— 7-methyl 685 Me 3-Br-Pyridin-5-yl- S—CH₂—C(CH₃)═CH—CH₂— 8-tert-butyl 686 Propyl Phenyl S—CH₂—C(CH₃)═CH—CH₂— 7-methyl 687 Me 2-Pyrazinyl- S—(CH₂)₃— 8-nitro 688 Me 2-Thienyl S—(CH₂)₃— 8-nitro 689 Me Phenyl S—(CH₂)₃— 8-cyano 690 Me 3-Jod-phenyl S—(CH₂)₄— 7-methoxy 691 Me Tetrazolyl- S—(CH₂)₃— 8-tert-butyl 692 Me 2-Pyrazinyl- S—(CH₂)₃— H 693 Me 2-Pyrazinyl- S—(CH₂)₃— 8-cyano 694 Me 2,5-Di-methyl-furanyl-3- S—(CH₂)₃— 8-tert-butyl 695 Me 4-Methylthiazol-5-yl S—(CH₂)₃— 7-methoxy 696 Phenyl 3-Benzthienyl- S—(CH₂)₃— 8-tert-butyl 697 Propyl Phenyl COO—(CH₂)₄— H 698 isoPropyl Phenyl S—CH₂—C(═CH₂)—CH₂ 7-methyl 699 Ethyl 3-Jod-phenyl S—CH₂—C(CH₃)═CH—CH₂— 8-cyano 700 Phenyl 2-Pyrazinyl- O—(CH₂)₃— 8-tert-butyl 701 Me 2-Me-4-Oxazolyl- S—CH₂—CH═CH—CH₂— 8-tert-butyl 702 isoPropyl Cyclohexyl- O—(CH₂)₈— 8-tert-butyl 703 Phenyl 3-Cyano-phenyl S—(CH₂)₃— 8-tert-butyl 704 Me Pyridin-3-yl- S—(CH₂)₃— 7-methoxy 705 Me 4-Methoxyphenyl S—(CH₂)₃— 8-tert-butyl 706 Me N-Propyl-tetrazolyl- S—(CH₂)3— 8-tert-butyl 707 Me 4-Methoxyphenyl S—(CH₂)₃— 7-chloro 708 Propyl Phenyl S—(CH₂)₃— 7-methoxy 709 Me 2-Thienyl S—(CH₂)₇— H 710 cycPropyl Phenyl (CH₂)₄— 7-methyl 711 Ethyl Phenyl S—(CH₂)₃— 8-nitro 712 cycPropyl Phenyl O—(CH₂)₃— 7-methyl 713 Me 4-Jod-phenyl S—CH₂—CH═CH—CH₂— 8-tert-butyl 714 Ethyl 4-Methylthiazol-5-yl S—CH₂—C(CH₃)═CH—CH₂— 8-cyano 715 Me 4-Methoxyphenyl S—CH₂—CH═CH—CH₂— H 716 Me Methylamino S—(CH₂)₃— 8-tert-butyl 717 isoPropyl 3-Thienyl S—(CH₂)₃— 8-tert-butyl 718 Me 3-Jod-phenyl S—(CH₂)3— 7-chloro 719 Butyl Phenyl (CH₂)₄— 7-methyl 720 Hexyl Phenyl (CH₂)₄— 7-methyl 721 isoPropyl 2-Thienyl CONH—(CH₂)₄— H 722 Me N-Methyl-2-Pyrrolyl- S—(CH₂)₃— 8-tert-butyl 723 Ethyl Phenyl S—(CH₂)₃— 7-chloroo

Examples of Pharmaceutical Administration Forms

A) Tablets

Tablets of the following composition were pressed on a tabletting machine in the customary manner

40 mg of the substance from Example 1

120 mg of corn starch

13.5 mg of gelatin

45 mg of lactose

2.25 mg of Aerosil® (chemically pure silicic acid in a submicroscopically fine dispersion)

6.75 mg of potato starch (as a 6% paste)

B) Sugar-coated Tablets

20 mg of the substance from Example 1

60 mg of core composition

70 mg of sugar-coating composition

The core composition consists of 9 parts of corn starch, 3 parts of lactose and 1 part of vinylpyrrolidone-vinyl acetate 60:40 copolymer. The sugar-coating composition consists of 5 parts of cane sugar, 2 parts of corn starch, 2 parts of calcium carbonate and 1 part of talc. The sugar-coated tablets which have been prepared in this way are then provided with enteric coating.

Biological Investigations—receptor binding studies

1) D₃ Binding Test

Cloned human D₃-receptor-expressing CCL 1,3 mouse fibroblasts, obtainable from Res. Biochemicals Internat. One Strathmore Rd., Natick, Mass. 01760-2418 USA, were used for the binding studies.

Cell Preparation

The D₃-expressing cells were multiplied in RPMI-1640 containing 10% fetal calf serum (GIBCO No. 041-32400 N); 100 U of penicillin/ml and 0.2% streptomycin (GIBO BRL, Gaithersburg, Md., USA). After 48 h, the cells were washed with PBS and incubated for 5 min with 0.05% trypsin-containing PBS. After that, the solution was neutralized with medium and the cells were collected by centrifuging at 300 g. In order to lyse the cells, the pellet was washed briefly with lysis buffer (5 mM Tris-HCl, pH 7.4, containing 10% glycerol) and after that incubated, at 4° C. for 30 min, at a concentration of 10⁷ cells/ml of lysis buffer. The cells were centrifuged at 200 g for 10 min and the pellet was stored in liquid nitrogen.

Binding Tests

For the D₃-receptor binding test, the membranes were suspended in incubation buffer (50 mM Tris-HCl, pH 7.4, containing 120 mM NaCl, 5 mM KC1, 2 mM CaCl₂, 2 mM MgCl₂, 10 μM quinolinol, 0.1% ascorbic acid and 0.1% BSA), at a concentration of approx. 10⁶ cells/250 μl of test mixture, and incubated at 30° C. for 0.1 nM ¹²⁵iodosulpiride in the presence and absence of the test substance. The nonspecific binding was determined using 10⁻⁶ M spiperone.

After 60 min, the free radioligand and the bound radioligand were separated by filtering through GF/B glass fiber filters (Whatman, England) on a Skatron cell harvester (Skatron, Lier, Norway), and the filters were washed with ice-cold Tris-HCl buffer, pH 7.4. The radioactivity which had collected on the filters was quantified using a Packard 2200 CA liquid scintillation counter.

The K_(i) values were determined by means of nonlinear regression analysis using the LIGAND program. The compound of example 1 has a K_(i) value for the binding toward the D₃ receptor of K_(i) =50 nM.

2) D₂ Binding Test

Cell Culture

HEK-293 cells possessing stably expressed human dopamine D2A receptors were cultured in RPMI 1640 containing Glutamix I™ and 25 mM HEPES containing 10% fetal calf serum albumin. All the media contained 100 units of penicillin per mol and 100 μg/ml of streptomycin/ml. The cells were maintained at 37° C. in a moist atmosphere containing 5% Co₂.

The cells were prepared for the binding studies by trypsinizing them (0.05% solution of trypsin) at room temperature for 3-5 minutes. After that, the cells were centrifuged at 250 g for 10 minutes and treated with lysis buffer (5 mM Tris-HCl, 10% glycerol, pH 7.4) at 4° C. for 30 minutes. After centrifuging at 250 g for 10 minutes, the residue was stored at −20° C. until used.

Receptor Binding Tests

Low affinity state dopamine D₂ receptor using ¹²⁵I-spiperone (81 TBq/mmbl, Du Pont de Nemours, Dreieich)

The test mixtures (1 ml) consisted of 1×10⁵ cells in incubation buffer (50 mM Tris, 120 mM NaCl, 5 mM KCl, 2 MM MgCl₂ and 2 mM CaCl₂, pH 7.4 with HCl) and 0.1 mM ¹²⁵I-spiperone (total binding) or additionally 1 μM haloperidol (nonspecific binding) or test substance.

After the test mixtures had been incubated at 25° C. for 60 minutes, they were filtered through GM/B glass filters (Whatman, England) on a Skatron cell harvester (from Zinsser, Frankfurt), and the filters were washed with ice-cold 50 mM Tris-HCl buffer, pH 7.4. The radioactivity: which had collected on the filters was quantified using a Packard 2200 CA liquid scintillation counter.

The results were evaluated as described in a).

The K_(i) values were determined by way of nonlinear regression analysis using the LIGAND program or by converting the IC₅₀ values using the Cheng and Prusoff formula.

In these tests, the compounds according to the invention exhibit very good affinities for the D₃ receptor (<1 μmolar, in particular <200 nmolar) and bind selectively to the D₃ receptor. 

We claim:
 1. A triazole compound of the formula I

where R¹ is H, C₁-C₆-alkyl, which may be substituted by OH, OC₁-C₆-alkyl, halogen or phenyl, C₃-C₆-cycloalkyl or phenyl; R² is H, C₁-C₆-alkyl, which may be substituted by OH, OC₁-C₆-alkyl, halogen or phenyl, C₁-C₆-alkoxy, C₁-C₆-alkylthio, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₆-cycloalkyl, halogen, CN, COOR³, CONR³R⁴, NR³R⁴, SO₂R³, SO₂NR³R⁴ or an aromatic radical which is selected from phenyl, naphthyl and a 5- or 6-membered heterocyclic radical having 1, 2, 3 or 4 heteroatoms which are selected, independently of each other, from O, N and S, with it being possible for the aromatic radical to have one or two substituents which are selected, independently of each other, from OH, C₁-C₆-alkyl, which may be substituted by OH, OC₁-C₆-alkyl, halogen or phenyl, C₁-C₆-alkoxy, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₆-cycloalkyl, halogen, CN, COR³, NR³R⁴, NO₂, SO₂R³, SO₂NR³R⁴ and phenyl which may be substituted by one or two radicals which are selected, independently of each other, from C₁-C₆-alkyl, C₁-C₆-alkoxy, NR³R⁴, CN, CF₃, CHF₂ or halogen; R³ and R⁴ are, independently of each other, H, C₁-C₆-alkyl, which may be substituted by OH, OC₁-C₆-alkyl, halogen or phenyl, or phenyl; A is C₄-C₁₀-alkylene or C₃-C₁₀-alkylene which comprises at least one group Z which is selected from O, S, CONR³, COO, CO, C₃-C₆-cycloalkyl and a double or triple bond; B is a radical of the following formulae (a) or (b):

X is CH₂ or CH₂CH₂; Y is CR₂ or O; R⁶ and R⁷ are, independently of each other, selected from H, C₁-C₆-alkyl, which may be substituted by halogen, C₁-C₆-alkylthio-C₁-C₆-alkyl, OH, C₁-C₆-alkoxy, C₂-C₆-alkenyl, halogen, CN, NO₂, SO₂R³, SO₂NR³R⁴ and CONR³R⁴, or a salt thereof with a physiologically tolerated acid.
 2. A compound as claimed in claim 1 of the formula I, where X and/or Y are CH₂.
 3. A compound as claimed in claim 1 of the formula I, where A is C₄-C₁₀-alkylene or C₃-C₁₀-alkylene which comprises at least one group Z which is selected from O, S, COO, CO, a double bond or triple bond and C₃-C₆-cycloalkyl.
 4. A compound as claimed in claim 1 of the formula I where A is C₄-C₁₀-alkylene or C₃-C₁₀-alkylene which comprises at least one group Z which is selected from O, S, a double bond and cyclohexyl.
 5. A compound as claimed in claim 1 of the formula I, where R² is an aromatic radical which is unsubstituted or has one or two substituents which are selected, independently of each other, from C₁-C₆-alkyl, OH, C₁-C₆-alkoxy, phenyl, CN and halogen.
 6. A compound as claimed in claim 1 of the formula I, where R² is H, C₁-C₆-alkyl, phenyl, thienyl, furanyl, pyridyl, pyrrolyl, thiazolyl or pyrazinyl.
 7. A compound as claimed in claim 1 of the formula I, where R¹ is H, C₁-C₆-alkyl or C₃-C₆-cycloalkyl.
 8. A compound as claimed in claim 1 of the formula I, where R⁶ and R⁷ are selected, independently of each other, from H, C₁-C₆-alkylthio-C₁-C₆-alkyl, halogen, CN, NO₂, So₂R³, SO₂NR³R⁴ and CONR³R⁴.
 9. A compound as claimed in claim 1 of the formula I, where R¹ is H, C₁-C₆-alkyl or phenyl, R² is H, C₁-C₆-alkyl, phenyl, thienyl, furanyl, tetrazolyl, pyrrolyl, thiazolyl or pyrazinyl, A is -SC₃-C₁₀-alkylene which may comprise a double bond, and R⁶ and R⁷ are selected from H, C₁-C₆-alkyl, C₁-C₆-alkoxy, halogen, SO₂NR₃R⁴, CN, NO₂ and CF_(3.)
 10. A pharmaceutical which comprises at least one compound as claimed in claim 1, where appropriate together with physiologically acceptable excipients and/or adjuvants.
 11. A triazole compound of formula I

where R¹ is H, C₁-C₆-alkyl, which may be substituted by OH, OC₁-C₆-alkyl, halogen or phenyl, C₃-C₆-cycloalkyl or phenyl; R² is H, C₁-C₆-alkyl, which may be substituted by OH, OC₁-C₆-alkyl, halogen or phenyl, C₁-C₆-alkoxy, C₁-C₆-alkylthio, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₆-cycloalkyl, halogen, CN, COOR³, CONR³R⁴, NR³R⁴, SO₂R³, SO₂NR³R⁴ or an aromatic radical which is selected from phenyl, naphthyl and a 5- or 6-membered heterocyclic radical having 1, 2, 3 or 4 heteroatoms which are selected, independently of each other, from O, N and S, with it being possible for the aromatic radical to have one or two substituents which are selected, independently of each other, from OH, C₁-C₆-alkyl, which may be substituted by OH, OC₁-C₆-alkyl, halogen or phenyl, C₁-C₆-alkoxy, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₆-cycloalkyl, halogen, CN, COR³, NR³R⁴, NO₂, SO₂R³, SO₂NR³R⁴ and phenyl which may be substituted by one or two radicals which are selected, independently of each other, from C₁-C₆-alkyl, C₁-C₆-alkoxy, NR³R⁴, CN, CF₃, CHF₂ or halogen; R³ and R⁴ are, independently of each other, H, C₁-C₆-alkyl, which may be substituted by OH, OC₁-C₆-alkyl, halogen or phenyl, or phenyl; A is C₄-C₁₀-alkylene or C₃-C₁₀-alkylene which comprises at least one group Z which is selected from O, S, CONR³, COO, CO, C₃-C₆-cycloalkyl and a double or triple bond; B is a radical of the following formulae (a) or (b):

X is CH₂ or CH₂CH₂; Y is CH₂; R⁶ and R⁷ are, independently of each other, selected from H, C₁-C₆-alkyl, which may be substituted by halogen, C₁-C₆-alkylthio-C₁-C₆-alkyl, OH, C₁-C₆-alkoxy, C₂-C₆-alkenyl, halogen, CN, NO₂, SO₂R³, SO₂NR³R⁴ and CONR³R⁴, or a salt thereof with a physiologically tolerated acid.
 12. The compound defined in claim 11, wherein X is CH₂.
 13. The compound defined in claim 11, wherein A is C₄-C₁₀-alkylene or C₃-C₁₀-alkylene which comprises at least one group Z which is selected from O, S, COO, CO, a double bond or triple bond and C₃-C₆-cycloalkyl.
 14. A compound as claimed in claim 11, wherein A is C₄-C₁₀-alkylene or C₃-C₁₀-alkylene which comprises at least one group Z which is selected from O, S, a double bond and cyclohexyl.
 15. A compound as claimed in claim 11, wherein R² is an aromatic radical which is unsubstituted or has one or two substituents which are selected, independently of each other, from C₁-C₆-alkyl, OH, C₁-C₆-alkoxy, phenyl, CN and halogen.
 16. A compound as claimed in claim 11, wherein R² is H, C₁-C₆-alkyl, phenyl, thienyl, furanyl, pyridyl, pyrrolyl, thiazolyl or pyrazinyl.
 17. A compound as claimed in claim 11, wherein R¹ is H, C₁-C₆-alkyl or C₃-C₆-cycloalkyl.
 18. A compound as claimed in claim 11, wherein R⁶ and R⁷ are selected, independently of each other, from H, C₁-C₆-alkylthio-C₁-C₆-alkyl, halogen, CN, NO₂, SO₂R³, SO₂NR³R⁴ and CONR³R⁴.
 19. A compound as claimed in claim 11, wherein R¹ is H, C₁-C₆-alkyl or phenyl, R² is H, C₁-C₆-alkyl, phenyl, thienyl, furanyl, tetrazolyl, pyrrolyl, thiazolyl or pyrazinyl, A is —SC₃-C₁₀-alkylene which may comprise a double bond, and R⁶ and R⁷ are selected from H, C₁-C₆-alkyl, C₁-C₆-alkoxy, halogen, SO₂NR³R⁴, CN, NO₂ and CF₃.
 20. A pharmaceutical which comprises at least one compound as claimed in claim 11, optionally together with physiologically acceptable excipients and/or adjuvants. 